Variant 11-92981507-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_005959.5(MTNR1B):c.284C>T(p.Pro95Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,614,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

MTNR1B
NM_005959.5 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 4.44

Variant links:

Genes affected

MTNR1B (HGNC:7464): (melatonin receptor 1B) This gene encodes one of two high affinity forms of a receptor for melatonin, the primary hormone secreted by the pineal gland. This gene product is an integral membrane protein that is a G-protein coupled, 7-transmembrane receptor. It is found primarily in the retina and brain although this detection requires RT-PCR. It is thought to participate in light-dependent functions in the retina and may be involved in the neurobiological effects of melatonin. [provided by RefSeq, Jul 2008]

MTNR1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.902

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MTNR1B	NM_005959.5 linkuse as main transcript	c.284C>T	p.Pro95Leu	missense_variant	2/2	ENST00000257068.3
MTNR1B	XM_011542839.3 linkuse as main transcript	c.284C>T	p.Pro95Leu	missense_variant	2/3
MTNR1B	XM_017017777.2 linkuse as main transcript	c.158C>T	p.Pro53Leu	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MTNR1B	ENST00000257068.3 linkuse as main transcript	c.284C>T	p.Pro95Leu	missense_variant	2/2	1	NM_005959.5	P1
MTNR1B	ENST00000528076.1 linkuse as main transcript	c.166-3300C>T		intron_variant		3
MTNR1B	ENST00000532482.1 linkuse as main transcript	c.*175C>T		3_prime_UTR_variant, NMD_transcript_variant	3/3	5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251416

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000279

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Diabetes mellitus type 2, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jan 29, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Uncertain

-0.020

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.46

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.014

MetaRNN

Pathogenic

0.90

MetaSVM

Uncertain

-0.17

MutationAssessor

Pathogenic

3.5

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-7.7

REVEL

Uncertain

0.45

Sift

Uncertain

0.0010

Sift4G

Benign

0.073

Polyphen

1.0

Vest4

0.82

MutPred

0.70

Gain of helix (P = 0.2059);

MPC

0.68

ClinPred

1.0

GERP RS

3.1

Varity_R

0.76

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over